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      Respiratory health and inflammatory markers - Exposure to respirable dust and quartz and chemical binders in Swedish iron foundries

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          Abstract

          Purpose

          To study the relationship between respirable dust, quartz and chemical binders in Swedish iron foundries and respiratory symptoms, lung function (as forced expiratory volume FEV 1 and vital capacity FVC), fraction of exhaled nitric oxide (FENO) and levels of club cell secretory protein 16 (CC16) and CRP.

          Methods

          Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Full shift sampling and examination were performed on the second or third day of a working week after a work free weekend, with additional sampling on the fourth or fifth day. Logistic, linear and mixed model analyses were performed including, gender, age, smoking, infections, sampling day, body mass index (BMI) and chemical binders as covariates.

          Results

          The adjusted average respirable quartz and dust concentrations were 0.038 and 0.66 mg/m 3, respectively. Statistically significant increases in levels of CC16 were associated with exposure to chemical binders (p = 0.05; p = 0.01) in the regression analysis of quartz and respirable dust, respectively. Non-significant exposure-responses were identified for cumulative quartz and the symptoms asthma and breathlessness. For cumulative chemical years, non-significant exposure–response were observed for all but two symptoms. FENO also exhibited a non significant exposure-response for both quartz and respirable dust. No exposure-response was determined for FEV 1 or FVC, CRP and respirable dust and quartz.

          Conclusions

          Our findings suggest that early markers of pulmonary effect, such as increased levels of CC16 and FENO, are more strongly associated with chemical binder exposure than respirable quartz and dust in foundry environments.

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          Most cited references44

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          Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker.

          Clara cell protein (CC16) is a 15.8-kDa homodimeric protein secreted in large amounts in airways by the non-ciliated bronchiolar Clara cells. This protein increasingly appears to protect the respiratory tract against oxidative stress and inflammation. In vitro, CC16 has been shown to modulate the production and/or the activity of various mediators of the inflammatory response including PLA2, interferon-gamma and tumour necrosis factor-alpha. CC16 has also been found to inhibit fibroblast migration or to bind various endogenous or exogenous substances such as polychlorobiphenyls (PCBs). This protective role is confirmed by studies on transgenic mice, showing that CC16 deficiency is associated with an increased susceptibility of the lung to viral infections and oxidative stress. In humans, a polymorphism of the CC16 gene, localized to a region linked to airway diseases, has recently been discovered in association with an increased risk of developing childhood asthma. Finally, CC16 also presents a major interest as a peripheral marker for assessing the integrity of the lung epithelium. The determination of CC16 in serum is a new non-invasive test to detect Clara cell damage or an increased epithelial permeability in various acute and chronic lung disorders.
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            Experimental exposure to wood smoke: effects on airway inflammation and oxidative stress.

            Particulate air pollution affects cardiovascular and pulmonary disease and mortality. A main hypothesis about the mechanisms involved is that particles induce inflammation in lower airways, systemic inflammation and oxidative stress. To examine whether short-term exposure to wood smoke in healthy subjects affects markers of pulmonary inflammation and oxidative stress. 13 subjects were exposed first to clean air and then to wood smoke in a chamber during 4-hour sessions, 1 week apart. The mass concentrations of fine particles at wood smoke exposure were 240-280 mug/m(3), and number concentrations were 95 000-180 000/cm(3), about half of the particles being ultrafine (<100 nm). Blood and breath samples were taken before and at various intervals after exposure to wood smoke and clean air and examined for exhaled nitric oxide and Clara cell protein in serum and urine, and malondialdehyde in exhaled breath condensate. Exposure to wood smoke increased alveolar nitric oxide 3 hours post-exposure while malondialdehyde levels in breath condensate were higher both immediately after and 20 hours after exposure. Serum Clara cell protein was increased 20 hours after exposure. Wood smoke at levels that can be found in smoky indoor environments caused an inflammatory response and signs of increased oxidative stress in the respiratory tract, especially in the lower airways.
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              A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects.

              Biomarkers associated with asthma aetiology and exacerbation have been sought to shed light on this multifactorial disease. One candidate is the serum concentration of the Clara cell secretory protein (CC16, sometimes referred to as CC10 or uteroglobin). In this review, we examine serum CC16's relation to asthma aetiology and exacerbation. There is evidence that acute exposures to certain pulmonary irritants can cause a transient increase in serum CC16 levels, and limited evidence also suggests that a transient increase in serum CC16 levels can be caused by a localized pulmonary inflammation. Research also indicates that a transient increase in serum CC16 is not associated with measurable pulmonary damage or impairment of pulmonary function. The biological interpretation of chronic changes in serum CC16 is less clear. Changes in serum CC16 concentrations (either transient or chronic) are not specific to any one agent, disease state, or aetiology. This lack of specificity limits the use of serum CC16 as a biomarker of specific exposures. To date, many of the critical issues that must be understood before serum CC16 levels can have an application as a biomarker of effect or exposure have not been adequately addressed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Investigation
                Role: Investigation
                Role: Investigation
                Role: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 November 2019
                2019
                : 14
                : 11
                : e0224668
                Affiliations
                [1 ] Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
                [2 ] Department of Medical Sciences, School of Medicine and Health, Örebro University, Örebro, Sweden
                [3 ] Inflammatory Response and Infection Susceptibility Centre (iRiSC), Örebro University, Örebro, Sweden
                [4 ] Unit of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
                Telethon Institute for Child Health Research, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-8166-7955
                Article
                PONE-D-19-17341
                10.1371/journal.pone.0224668
                6824619
                31675355
                2f0a7c81-0df1-4bd2-864f-bf252d84c175
                © 2019 Andersson et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 June 2019
                : 19 October 2019
                Page count
                Figures: 0, Tables: 6, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100006636, Forskningsrådet om Hälsa, Arbetsliv och Välfärd;
                Award ID: 2014-0802
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003170, Stiftelsen för Kunskaps- och Kompetensutveckling;
                Award ID: 20150036, ProSpekt14
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003509, Örebro Universitet;
                Award ID: ORU 2.2.1-4060/2013
                Award Recipient :
                This study was supported by the Swedish Research Council for Health, Working Life and Welfare (FORTE) grant number 2014-0802 to HW. AH and AP were supported by Postdoctoral Research fellowships from the Knowledge Foundation (Ref no: 20150036, ProSpekt14) and from Örebro University (Strategic grant, Ref no: ORU 2.2.1-4060/2013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Data cannot be shared publicly due to legal restrictions imposed by Swedish Law regarding identifiable data. Data access requests can be directed to Etikprövningsmyndigheten i Uppsala (Swedish Ethical Review Authority in Uppsala): https://etikprovningsmyndigheten.se/ or registrator@ 123456etikprovning.se .

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